Phenotypes Associated with This Genotype

Genotype
MGI:3603515

• Allelic Composition: Ighmbp2^nmd-2J/Ighmbp2^nmd-2J
• Genetic Background: B6.BKS-Ighmbp2^nmd-2J/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:90418 )

• at 62 days for males and 76 days for females

• maximum life span is 138 days for females

cardiovascular system

abnormal heart morphology ( J:90418 )

abnormal myocardial fiber morphology ( J:90418 )

• few desmosomes

abnormal intercalated disk morphology ( J:90418 )

• attenuated

myocardial fiber degeneration ( J:90418 )

• degenerating and apoptotic

• nuclear blebbing

myocardium necrosis ( J:90418 )

dilated heart atrium ( J:90418 )

abnormal heart valve morphology ( J:90418 )

• secondary valvular insufficiency

abnormal heart ventricle morphology ( J:90418 )

thin ventricular wall ( J:90418 )

dilated heart ventricle ( J:90418 )

cardiac interstitial fibrosis ( J:90418 )

abnormal cardiovascular system physiology ( J:90418 )

dilated cardiomyopathy ( J:90418 )

• as early as 4-6 weeks of age

• pale, flaccid, enlarged hearts with one or more thrombi

increased heart rate variability ( J:90418 )

decreased heart rate ( J:90418 )

abnormal impulse conducting system conduction ( J:90418 )

prolonged PR interval ( J:90418 )

• prolonged P-R interval

prolonged P wave ( J:90418 )

• attenuated, sometimes split

abnormal QRS complex ( J:90418 )

• prolonged and attenuated R waves

decreased systemic arterial systolic blood pressure ( J:90418 )

• decreased lower end systolic blood pressure

nervous system

abnormal Schwann cell morphology ( J:92862 )

• frequently show indications of secondary myelin degeneration

• sometimes lacking axons

abnormal innervation pattern to muscle ( J:92862 )

• axon numbers in quadriceps nerves significantly decrease with age from 3 weeks on, 40% reduction by 12-14 weeks

motor neuron degeneration ( J:90418 )

• significant neuronal loss by 7 weeks in all lumbar ventral roots examined

• 56% of L4 motor axons lost

• numerous dystrophic axons in ventral roots

• most losses are of large axons

• 40% loss of small caliber axons

abnormal axon morphology ( J:92862 )

• vacuolation occurs during the course of myelination or after myelination

• abnormal cytoskeletons

• process of myelination normal

abnormal neuromuscular synapse morphology ( J:92862 )

• denervation of motor endplates increases dramatically as motor neuron degeneration progresses

muscle

abnormal myocardial fiber morphology ( J:90418 )

• few desmosomes

abnormal intercalated disk morphology ( J:90418 )

• attenuated

myocardial fiber degeneration ( J:90418 )

• degenerating and apoptotic

• nuclear blebbing

myocardium necrosis ( J:90418 )

dilated cardiomyopathy ( J:90418 )

• as early as 4-6 weeks of age

• pale, flaccid, enlarged hearts with one or more thrombi

skeletal muscle fiber atrophy ( J:90418 )

• severe muscle wasting and hind limb contracture

increased variability of skeletal muscle fiber size ( J:90418 )

• variable fiber size

centrally nucleated skeletal muscle fibers ( J:90418 )

• centralized nuclei in myocytes

abnormal diaphragm morphology ( J:92862 )

• development of diaphragmatic muscle degeneration occurs late, around 8-14 weeks

skeletal muscle interstitial fibrosis ( J:90418 )

• and fatty infiltration

muscle degeneration ( J:90418 )

• severe diffuse myocyte degeneration and regeneration

behavior/neurological

decreased grip strength ( J:90418 )

• much shorter latency to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top much shorter latence to fall when suspended from a wire cage top

respiratory system

pulmonary edema ( J:90418 )

• consolidation of lungs

pleural effusion ( J:90418 )

decreased pulmonary respiratory rate ( J:90418 )

• reduced breathing rate (bradypnea)

growth/size/body

weight loss ( J:90418 )

homeostasis/metabolism

increased circulating creatine kinase level ( J:90418 )

• 3-7 days prior to clearly evident clinical signs of heart disease, total plasma CK and cardiac-specific CK-MB levels in 5- to 9-week-old mice become significantly elevated

pulmonary edema ( J:90418 )

• consolidation of lungs

pleural effusion ( J:90418 )

cellular

cardiac interstitial fibrosis ( J:90418 )

abnormal cell cytoskeleton morphology ( J:92862 )

• abnormal cytoskeletons in axons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive distal hereditary motor neuronopathy 1		DOID:0111064	OMIM:604320	J:92862